PoppiE: Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
Study Details
Study Description
Brief Summary
A randomized controlled trial to determine the effect of reducing iodine from vitamin and mineral supplements for pregnant women who have adequate iodine intakes (>165 μg/d from food alone) on cognitive development of children at 24 months of age.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
It is known that severe iodine deficiency during pregnancy leads to profound intellectual disabilities in the child. Following results of a 2004 national survey of school-aged children showing that mild iodine deficiency had re-emerged in the south-eastern parts of Australia, the Australian government mandated the addition of iodine to salt used in bread making to increase population iodine intake. It is also recommended that all pregnant and lactating women take an additional iodine supplement containing 150 µg/d of iodine.
Since this time, further evidence has emerged from cohort studies that children born to women with high iodine intake (as well as low iodine intake) have poorer neurodevelopmental scores, suggesting that more tailored supplementation may be a better strategy. Our PoppiE trial will determine if limiting iodine supplementation in women who already consume adequate iodine from food, improves cognitive scores in early childhood.
A total of 754 pregnant women from around Australia who are ≤13 weeks of gestation will be enrolled and randomised to receive a standard prenatal vitamin and mineral supplement with a reduced amount of iodine (20 μg - intervention) or a standard prenatal vitamin and mineral supplement with 200 μg of iodine (control). The control supplement contains a level of iodine to match the amount in most commonly used vitamin and mineral supplements sold in Australia. Infant neurodevelopment at 24 months of age will be assessed using the Bayley-IV and conducted at participating centres or a location convenient to the family.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Low Iodine Supplement Iodine (potassium iodide) 20 μg Beta carotene (All trans-beta- carotene) 1500 μg; Vitamin E (dl-alphatocopheryl acetate) 13.5 mg AT; Vitamin D3 (cholecalciferol) 10 μg; Vitamin C (ascorbic acid granular) 60 mg; Niacinamide 18 mg; Pantothenic acid (calcium d- pantothenate) 6 mg; Vitamin B6 (DC pyridoxine hydrochloride) 1.9 mg; Vitamin B1 (thiamine mononitrate) 1.4 mg; Vitamin B2 (riboflavin) 1.4 mg; Biotin 30 μg; Vitamin B12 (methyl-cobalamin) 2.6 μg; Folic Acid 0.4 mg; Levomefolic acid 0.1 mg; Calcium (carbonate DC) 250 mg; Magnesium (oxide granular) 50 mg; Iron (ferrous fumarate) 20 mg; Zinc (oxide) 10 mg; Manganese (sulphate) 2 mg; Copper (sulphate) 1 mg; Selenium (rice chelate) 30 μg |
Combination Product: Low Iodine Supplement
Multivitamin and mineral supplement with reduced iodine
|
| Active Comparator: Standard Iodine Supplement Iodine (potassium iodide) 200 μg Beta carotene (All trans-beta- carotene) 1500 μg; Vitamin E (dl-alphatocopheryl acetate) 13.5 mg AT; Vitamin D3 (cholecalciferol) 10 μg; Vitamin C (ascorbic acid granular) 60 mg; Niacinamide 18 mg; Pantothenic acid (calcium d- pantothenate) 6 mg; Vitamin B6 (DC pyridoxine hydrochloride) 1.9 mg; Vitamin B1 (thiamine mononitrate) 1.4 mg; Vitamin B2 (riboflavin) 1.4 mg; Biotin 30 μg; Vitamin B12 (methyl-cobalamin) 2.6 μg; Folic Acid 0.4 mg; Levomefolic acid 0.1 mg; Calcium (carbonate DC) 250 mg; Magnesium (oxide granular) 50 mg; Iron (ferrous fumarate) 20 mg; Zinc (oxide) 10 mg; Manganese (sulphate) 2 mg; Copper (sulphate) 1 mg; Selenium (rice chelate) 30 μg |
Combination Product: Standard Iodine Supplement
Multivitamin and mineral supplement with standard amount of iodine to match current leading brands of prenatal supplements
|
Outcome Measures
Primary Outcome Measures
- Infant Developmental quotient (DQ) [24 months of age]
The Bayley Scales of Infant and Toddler Development, 4th Edition Cognitive Scale score has a mean of 100 and standard deviation of 15, where higher scores indicate a better outcome. As the Bayley scales are age-standardized scales the exact minimum and maximum score depends on the exact age of the child at the time of the assessment, hence we have instead provided the mean and standard deviation (as is the norm when reporting standardized psychometric assessments).
Secondary Outcome Measures
- Language development of infants using Bayley-IV [24 months of age]
The Bayley Scales of Infant and Toddler Development, 4th Edition Language Scale score has a mean of 100 and standard deviation of 15, where higher scores indicate a better outcome.
- Motor development of infants [24 months of age]
The Bayley Scales of Infant and Toddler Development, 4th Edition Motor Scale score has a mean of 100 and standard deviation of 15, where higher scores indicate a better outcome.
- Behavioral and emotional development [24 months of age]
Behavioral and emotional development of infants using the Infant Toddler Social Emotional Assessment (ITSEA). The Infant-Toddler Social & Emotional Assessment scale has range of 0-100 where higher T scores indicate a worse outcome.
- Health service utilization [24 months of age]
Health service utilisation of children assessed through data linkage of the Medicare Benefits Schedule, Pharmaceutical Benefits Scheme to evaluate the cost effectiveness of the intervention.
- Length of gestation [Birth]
The gestational age in days at birth (or other event of interest) will be determined from the estimated date of delivery using the equation [280 - (estimated date of delivery - date of birth)].
- Infant Birth Anthropometrics [Birth]
Infant weight, length and head circumference will be analysed, using both the raw measurements and Z-scores for corresponding gestational age and sex, using means and standard deviations.
- Admission to special care baby unit (level 2 nursery). [The neonatal period including birth to 28 days of age]
Any admission to a special care baby unit or level 2 nursery up to 28 days post birth.
- Thyroid stimulating hormone (TSH) level [Within 5 days of birth]
Ascertained from Neonatal Screening Test
- Infant Anthropometrics [24 months of age]
Average weight, height and head circumference measurements at 24 months of age will be converted to z-scores using WHO growth standards. For preterm infants, corrected age at the time of the measurement rather than chronological age will be used in deriving the z-scores.
Other Outcome Measures
- Proportion of participants with pre-eclampsia [At any time throughout current pregnancy]
Clinical diagnosis of pre-eclampsia as recorded in the participants handheld record.
- Proportion of participants with induction of labour and reason for induction. [Delivery]
As recorded in the participants handheld record.
- Proportion of participants with postpartum hemorrhage [Within 24 hours of delivery of the infant]
Clinical diagnosis of postpartum hemorrhage as recorded in the participants handheld record.
- Proportion of participants with gestational diabetes [At any time throughout current pregnancy]
Clinical diagnosis of gestational diabetes as recorded in the participants handheld record.
- Proportion of participants with induced labour [Delivery]
As recorded in the participants handheld record.
- Proportion of participants with vaginal delivery [Delivery]
Vaginal or caesarean delivery
- Proportion of Maternal Adverse Events per group [From the date of randomization until delivery of the infant (up to 40 weeks)]
Side effects and tolerability of supplements will be assessed through routine data collection.
- Proportion of Maternal Serious Adverse Events per group [From the date of randomization until the date of delivery (up to 40 weeks)]
Maternal admissions to intensive care during the intervention period. Maternal death in the intervention period.
- Proportion of Fetal/Infant Serious Adverse Events [From the date of randomization until the infant is 24 months of age (up to 144 weeks)]
Fetal Mortality (after randomisation and prior to birth) including; miscarriage/terminations (pregnancy loss <20 weeks of gestation); stillbirth (intrauterine fetal death ≥20 weeks of gestation). Infant Mortality including; neonatal death (death of a live born infant in the first 28 days of life); infant death (death of an infant after the first 28 days of life). Major congenital anomalies.
- Economic Evaluation [From the date of randomization until the infant is 24 months of age (up to 144 weeks)]
A within-trial cost-effectiveness analysis will be conducted comparing costs and outcomes of the trial arms. The analysis will take into account a range of cost items including cost of interventions (i.e., dietary supplements) and cost of eligibility screening. Medicare data and data held by the State departments of health will be used to estimate direct health care costs associated with the management of poor developmental health outcomes over the study period including pharmaceuticals, out of hospital services (e.g., doctor visits), and hospital services (including emergency department presentations).
- Urinary Iodine Concentration [At baseline (enrolment <13 weeks of gestation) and mid-pregnancy (28 weeks of gestation)]
At baseline, median iodine concentration by state will be determined to confirm state differences in iodine status that have been previously identified and to determine balance between the two treatment groups. At 28 weeks we will examine median UIC by treatment group to assess group compliance and the success of the intervention.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Pregnant women ≤13 weeks of gestation.
-
Consume greater than 165 µg/d of iodine from food alone based on our validated Iodine Specific Food Frequency Questionnaire (I-FFQ).
-
English is main language spoken at home as child will need to understand and take instruction in English to participate in the neurodevelopmental assessment.
-
Able to give informed consent.
Exclusion Criteria:
-
Known history of thyroid disease.
-
Previous child diagnosed with thyroid dysfunction.
-
Carrying a fetus with a known or suspected congenital abnormality.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | South Australian Health and Medical Research Institute | North Adelaide | South Australia | Australia | 5081 |
Sponsors and Collaborators
- South Australian Health and Medical Research Institute
- Women's and Children's Hospital, Australia
- Flinders Medical Centre
- Mater Mothers' Hospital
- The Royal Women's Hospital
- Royal North Shore Hospital
Investigators
- Principal Investigator: Karen P Best, PhD, South Australian Health and Medical Research Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PoppiE